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Biomedical subjects

Rune Blomhoff

Publications and source records attributed to Rune Blomhoff.

46 records · Page 3Linked to original sources
PubMed2003

Several culinary and medicinal herbs are important sources of dietary antioxidants.

We assessed the contribution of culinary and medicinal herbs to the total intake of dietary antioxidants. Our results demonstrate that there is more than a 1000-fold difference among antioxidant concentrations of various herbs. Of the dried culinary herbs tested, oregano, sage, peppermint, garden thyme, lemon balm, clove, allspice and cinnamon as well as the Chinese medicinal herbs Cinnamomi cortex and Scutellariae radix all contained very high concentrations of antioxidants (i.e., >75 mmol/100 g). In a normal diet, intake of herbs may therefore contribute significantly to the total intake of plant antioxidants, and be an even better source of dietary antioxidants than many other food groups such as fruits, berries, cereals and vegetables. In addition, the herbal drug, Stronger Neo-Minophagen C, a glycyrrhizin preparation used as an intravenous injection for the treatment of chronic hepatitis, boosts total antioxidant intake. It is tempting to speculate that several of the effects due to these herbs are mediated by their antioxidant activities.

Antioxidants↗
PubMed2003

Berry intake increases the activity of the gamma-glutamylcysteine synthetase promoter in transgenic reporter mice.

A diet rich in fruit and vegetables is associated with decreased risk of disease. One possible mechanism for this is that dietary antioxidants positively regulate protective genes. Toward our goal to identify bioactive compounds with such functions in plants, we developed transgenic mice that express luciferase controlled by the gamma-glutamylcysteine synthetase heavy subunit (GCS(h)) promoter. Mice that consumed a nonpurified diet ad libitum were supplemented with juices or extracts of antioxidant-rich berries for 42 h or 3-4 wk. The treatments generally increased luciferase activity in brain and skeletal muscle and decreased it in liver compared with controls fed water. The same overall pattern was also found in mice fed ellagic acid (EA), a phenolic acid found in many berries. This change in GCS(h) promoter activity after berry treatment occurred in only approximately 50% of the mice, indicating that they were either responders or nonresponders. Our results demonstrate for the first time that berry extracts rich in polyphenols and EA can induce GCS(h) in vivo. The induction of protective enzymes may be important for the chemopreventive effects of fruits and vegetables.

Animals↗
PubMed2003

Identification of novel roles of the cytochrome p450 system in early embryogenesis: effects on vasculogenesis and retinoic Acid homeostasis.

The cytochrome P450-dependent monooxygenase system catalyzes the metabolism of xenobiotics and endogenous compounds, including hormones and retinoic acid. In order to establish the role of these enzymes in embryogenesis, we have inactivated the system through the deletion of the gene for the electron donor to all microsomal P450 proteins, cytochrome P450 reductase (Cpr). Mouse embryos homozygous for this deletion died in early to middle gestation (approximately 9.5 days postcoitum [dpc]) and exhibited a number of novel phenotypes, including the severe inhibition of vasculogenesis and hematopoiesis. In addition, defects in the brain, limbs, and cell types where CPR was shown to be expressed were observed. Some of the observed abnormalities have been associated with perturbations in retinoic acid homeostasis in later embryogenesis. Consistent with this possibility, embryos at 9.5 dpc had significantly elevated levels of retinoic acid and reduced levels of retinol. Further, some of the observed phenotypes could be either reversed or exacerbated by decreasing or increasing maternal retinoic acid exposure, respectively. Detailed analysis demonstrated a close relationship between the observed phenotype and the expression of genes controlling vasculogenesis. These data demonstrate that the cytochrome P450 system plays a key role in early embryonic development; this process appears to be, at least in part, controlled by regional concentrations of retinoic acid and has profound effects on blood vessel formation.

Animals↗
PubMed2003

Strong in vivo activation of NF-kappaB in mouse lenses by classic stressors.

PURPOSE: To examine the in vivo activation of nuclear factor (NF)-kappaB in mouse lens epithelia by using bacterial lipopolysaccharide (LPS), tumor necrosis factor (TNF)-alpha, and UV-B radiation. METHODS: Transgenic mice containing the NF-kappaB-luciferase reporter were injected with LPS, TNF-alpha or, exposed to UV-B. After various exposure times, the mice were killed, and ocular, liver, lung, kidney, spleen, and skin tissue were obtained. Tissue homogenates were examined for luciferase activity with a luminometer. Groups of mice were also imaged in vivo through a light-intensified camera system to assess NF-kappaB activity. RESULTS: LPS- and TNF-alpha injected NF-kappaB-luciferase transgenic mice yielded 20- to 40-fold increases in lens NF-kappaB activity, similar to other LPS- and TNF-alpha-responsive organs. Peak NF-kappaB activity occurred 6 hours after injection of TNF-alpha and 12 hours after injection of LPS. Peak activities were, respectively, 3 and 6 hours later than that in other tissues. Mice exposed to 360 J/m(2) of UV-B exhibited a 16-fold increase in NF-kappaB activity 6 hours after exposure, which are characteristics similar to TNF-alpha-exposed mice. In vivo imaging of transgenic mice exposed to LPS, TNF-alpha, and UV-B radiation demonstrated a similarity between in vitro and in vivo measurements of NF-kappaB activity. CONCLUSIONS: In NF-kappaB-luciferase transgenic mice, NF-kappaB activity occurs in lens epithelial tissue and is activated when the intact mouse is exposed to bacterial LPS, TNF-alpha, or UV-B. Lens epithelial NF-kappaB kinetics were comparable to those of other tissues, indicating that NF-kappaB may play a role in progression or arrest of lens disorders.

Animals↗
PubMed2002

Flavonoids increase the intracellular glutathione level by transactivation of the gamma-glutamylcysteine synthetase catalytical subunit promoter.

Fruits and vegetables protect against cancer by so far not well-characterized mechanisms. One likely explanation for this effect is that dietary plants contain substances able to control basic cellular processes such as the endogenous defense against oxidative stress. Oxidative stress is pivotal in many pathological processes and reduced oxidative stress is implicated in prevention of disease. Our results demonstrate that extract from onion and various flavonoids induce the cellular antioxidant system. Onion extract and quercetin were able to increase the intracellular concentration of glutathione by approximately 50%. Using a reporter construct where reporter expression is driven by the gamma-glutamylcysteine synthetase (GCS) heavy subunit (GCS(h)) promoter we show that onion extract, quercetin, kaempferol, and apigenin increased reporter gene activity, while a fourth flavonoid, myricetin and sugar conjugates of quercetin were unable to increase reporter expression. Quercetin was also able to induce a distal part of the GCS(h) promoter containing only two antioxidant-response/electrophile-response elements (ARE/EpRE). Our data strongly suggest that flavonoids are important in the regulation of the intracellular glutathione levels. This effect may be exerted in part through GCS gene regulation, and may also contribute to the disease-preventing effect of fruits and vegetables.

Animals↗
PubMed2002

In vivo imaging of NF-kappa B activity.

A wide range of human disorders involves inappropriate regulation of NF-kappaB, including cancers and numerous inflammatory conditions. Toward our goal to define mechanisms through which NF-kappaB leads to the development of disease, we have developed transgenic mice that express luciferase under the control of NF-kappaB, enabling real-time in vivo imaging of NF-kappaB activity in intact animals. We show that in the absence of extrinsic stimulation, strong luminescence is evident in lymph nodes in the neck region, thymus, and Peyer's patches. Treating mice with TNF-alpha, IL-1alpha, or LPS increased the luminescence in a tissue-specific manner, with the strongest activity observed in skin, lungs, spleen, Peyer's patches, and the wall of the small intestine. Liver, kidney, heart, muscle, and adipose tissue displayed less intense activities. Also, exposure of skin to a low dose of UV radiation increased luminescence in the exposed areas. Furthermore, induction of chronic inflammation resembling rheumatoid arthritis produced strong NF-kappaB activity in the affected joints, as revealed by in vivo imaging. Thus, we have developed a versatile model for monitoring NF-kappaB activation in vivo.

Animals↗
PubMed2002

Vitamins A and E in serum in relation to weight and lung function in patients with advanced pulmonary disease.

The objective of the study was to examine whether serum concentrations of retinol (vitamin A) and alpha-, beta-, and gamma-tocopherols (vitamin E) are affected by underweight and weight gain. The analysis was carried out in underweight (n = 42, of whom 24 had chronic obstructive pulmonary disease) and normal-weight (n = 29, of whom 16 had chronic obstructive pulmonary disease) candidates for lung transplantation before and after dietary intervention for weight gain. In all the patients, serum concentrations of retinol at baseline and changes in retinol were positively associated with body mass index (unstandardized regression coefficient, b = 0.03; p = 0.05) and an increase in weight (b = 0.09, p = 0.02) after dietary intervention, respectively. At baseline, serum retinol concentrations were positively correlated with forced vital capacity (b = 0.24, p < 0.05) and forced expiratory volume in one second (b = 0.17, p < 0.05). In patients with chronic obstructive pulmonary disease (COPD), tocopherols were higher in the underweight patients than in the normal-weight ones, while it was an opposite tendency in patients with other lung diseases. Only in patients with lung diseases other than COPD was there found a positive association between tocopherols and lung gas diffusion. In patients with other diagnoses compared with patients with COPD, a positive change in serum tocopherol status after weight gain was suggested.

Body Mass Index↗
PubMed2002

A systematic screening of total antioxidants in dietary plants.

A predominantly plant-based diet reduces the risk for development of several chronic diseases. It is often assumed that antioxidants contribute to this protection, but results from intervention trials with single antioxidants administered as supplements quite consistently do not support any benefit. Because dietary plants contain several hundred different antioxidants, it would be useful to know the total concentration of electron-donating antioxidants (i.e., reductants) in individual items. Such data might be useful in the identification of the most beneficial dietary plants. We have assessed systematically total antioxidants in a variety of dietary plants used worldwide, including various fruits, berries, vegetables, cereals, nuts and pulses. When possible, we analyzed three or more samples of dietary plants from three different geographic regions in the world. Total antioxidants was assessed by the reduction of Fe(3+) to Fe(2+) (i.e., the FRAP assay), which occurred rapidly with all reductants with half-reaction reduction potentials above that of Fe(3+)/Fe(2+). The values, therefore, expressed the corresponding concentration of electron-donating antioxidants. Our results demonstrated that there is more than a 1000-fold difference among total antioxidants in various dietary plants. Plants that contain most antioxidants included members of several families, such as Rosaceae (dog rose, sour cherry, blackberry, strawberry, raspberry), Empetraceae (crowberry), Ericaceae (blueberry), Grossulariaceae (black currant), Juglandaceae (walnut), Asteraceae (sunflower seed), Punicaceae (pomegranate) and Zingiberaceae (ginger). In a Norwegian diet, fruits, berries and cereals contributed 43.6%, 27.1% and 11.7%, respectively, of the total intake of plant antioxidants. Vegetables contributed only 8.9%. The systematic analysis presented here will facilitate research into the nutritional role of the combined effect of antioxidants in dietary plants.

Antioxidants↗
PubMed2002

Gene expression regulation by retinoic acid.

Over the last quarter century, more than 532 genes have been put forward as regulatory targets of retinoic acid. In some cases this control is direct, driven by a liganded heterodimer of retinoid receptors bound to a DNA response element; in others, it is indirect, reflecting the actions of intermediate transcription factors, non-classical associations of receptors with other proteins, or even more distant mechanisms. Given the broad range of scientific questions continually under investigation, researchers do not always have occasion to classify target genes along these lines. However, our understanding of the genetic role of retinoids will be enhanced if such a distinction can be made for each regulated gene. We have therefore evaluated published data from 1,191 papers covering 532 genes and have classified these genes into four categories according to the degree to which an hypothesis of direct versus indirect control is supported overall. We found 27 genes that are unquestionably direct targets of the classical pathway in permissive cellular contexts (Category 3 genes), plus 105 genes that appear to be candidates, pending the results of specific additional experiments (Category 2). Data on another 267 targets are not evocative of direct or indirect regulation either way, although control by retinoic acid through some mechanism is clear (Category 1). Most of the remaining 133 targets seem to be regulated indirectly, usually through a transcriptional intermediary, in the contexts studied so far (Category 0).

Animals↗